Chiral 1,3-aminoalcohols are important intermediates in the synthesis of various pharmaceutical products and product candidates, yet the preparation of these compounds remains a significant synthetic challenge to chemists. Gaining control over the stereochemistry of chiral centers at both the alcohol and amine (or in the cases in which only the alcohol- or amine- bearing carbon is chiral, a single chiral center) is the key to the production of these important chemical intermediates.
Chiral 1,3-aminoalcohols have potential applications both as pharmaceutically-active compounds, agricultural chemicals, chiral intermediates, and chiral auxiliary agents. For example, U.S. Pat. No. 3,668,199 describes novel 1,3-aminoalcohols having potential applications as anti-diabetic agents and diuretics. In the preparation of these compounds according to the method described in U.S. Pat. No. 3,668,199, a diketone is first converted into a keto-enamine, followed by catalytic hydrogenation of the keto-enamine using a platinum catalyst or similar. This method has the limitation that the 1,3-aminoalcohols are not produced in optically-pure form and the amino group must be a dialkylamine. U.S. Pat. No. 5,200,561 describes a process for producing optically active amines, including aminoalcohols. This method reacts an oxime with a metal borohydride compound complexed to a different optically-active amine. This method is costly, and further, requires that another optically active amine be used to form the borohydride complex in order to produce the desired optically active amine. Classical methods involving the formation of diastereomeric salts may also be employed to produce optically active 1,3-aminoalcohols; these resolution procedures require the use of an optically active acid to form the diastereomeric salt. The maximum theoretical yield in this method is only 50%, and in actual practice the yield is significantly lower. Thus, previously-described methods for the production of 1,3-aminoalcohols have limitations in scope, efficiency, chiral purity, and yield. An efficient method for the production of 1,3-aminoalcohols of high optical purity would facilitate the production of a number of pharmaceutical intermediates and chiral auxiliaries, and would be greatly desired.